Molecular cloning of FOG-2: a modulator of transcription factor GATA-4 in cardiomyocytes.

GATA transcription factors are important regulators of both hematopoiesis (GATA-1/2/3) and cardiogenesis (GATA-4) in mammals. The transcriptional activities of the GATA proteins are modulated by their interactions with other transcription factors and with transcriptional coactivators and repressors. Recently, two related zinc finger proteins, U-shaped (USH) and Friend of GATA-1 (FOG) have been reported to interact with the GATA proteins Pannier and GATA-1, respectively, and to modulate their transcriptional activities in vitro and in vivo. In this report, we describe the molecular cloning and characterization of a third FOG-related protein, FOG-2. FOG-2 is an 1,151 amino acid nuclear protein that contains eight zinc finger motifs that are structurally related to those of both FOG and USH. FOG-2 is first expressed in the mouse embryonic heart and septum transversum at embryonic day 8.5 and is subsequently expressed in the developing neuroepithelium and urogenital ridge. In the adult, FOG-2 is expressed predominately in the heart, brain, and testis. FOG-2 associates physically with the N-terminal zinc finger of GATA-4 both in vitro and in vivo. This interaction appears to modulate specifically the transcriptional activity of GATA-4 because overexpression of FOG-2 in both NIH 3T3 cells and primary rat cardiomyocytes represses GATA-4-dependent transcription from multiple cardiac-restricted promoters. Taken together, these results implicate FOG-2 as a novel modulator of GATA-4 function during cardiac development and suggest a paradigm in which tissue-specific interactions between different FOG and GATA proteins regulate the differentiation of distinct mesodermal cell lineages.

[1]  J. Turner,et al.  Cloning and characterization of mCtBP2, a co‐repressor that associates with basic Krüppel‐like factor and other mammalian transcriptional regulators , 1998, The EMBO journal.

[2]  R. Viger,et al.  Transcription factor GATA-4 is expressed in a sexually dimorphic pattern during mouse gonadal development and is a potent activator of the Müllerian inhibiting substance promoter. , 1998, Development.

[3]  R. Schwartz,et al.  GATA-4 and Nkx-2.5 Coactivate Nkx-2 DNA Binding Targets: Role for Regulating Early Cardiac Gene Expression , 1998, Molecular and Cellular Biology.

[4]  Youngsook Lee,et al.  The Cardiac Tissue-Restricted Homeobox Protein Csx/Nkx2.5 Physically Associates with the Zinc Finger Protein GATA4 and Cooperatively Activates Atrial Natriuretic Factor Gene Expression , 1998, Molecular and Cellular Biology.

[5]  Jeffrey Robbins,et al.  A Calcineurin-Dependent Transcriptional Pathway for Cardiac Hypertrophy , 1998, Cell.

[6]  S. Orkin,et al.  Failure of megakaryopoiesis and arrested erythropoiesis in mice lacking the GATA-1 transcriptional cofactor FOG. , 1998, Genes & development.

[7]  P. Simpson,et al.  Transcriptional activity of pannier is regulated negatively by heterodimerization of the GATA DNA-binding domain with a cofactor encoded by the u-shaped gene of Drosophila. , 1997, Genes & development.

[8]  R. J. Hill,et al.  end-1 encodes an apparent GATA factor that specifies the endoderm precursor in Caenorhabditis elegans embryos. , 1997, Genes & development.

[9]  D. Durocher,et al.  The cardiac transcription factors Nkx2‐5 and GATA‐4 are mutual cofactors , 1997, The EMBO journal.

[10]  S. Orkin,et al.  FOG, a Multitype Zinc Finger Protein, Acts as a Cofactor for Transcription Factor GATA-1 in Erythroid and Megakaryocytic Differentiation , 1997, Cell.

[11]  M. Fishman,et al.  Fashioning the vertebrate heart: earliest embryonic decisions. , 1997, Development.

[12]  A. Bassuk,et al.  Physical interactions between Ets and NF-kappaB/NFAT proteins play an important role in their cooperative activation of the human immunodeficiency virus enhancer in T cells , 1997, Journal of virology.

[13]  E. Olson,et al.  Requirement of the transcription factor GATA4 for heart tube formation and ventral morphogenesis. , 1997, Genes & development.

[14]  K Sigrist,et al.  GATA4 transcription factor is required for ventral morphogenesis and heart tube formation. , 1997, Genes & development.

[15]  E. Morrisey,et al.  GATA-5: a transcriptional activator expressed in a novel temporally and spatially-restricted pattern during embryonic development. , 1997, Developmental biology.

[16]  J. Leiden,et al.  Transcription factor GATA-3 is required for development of the T-cell lineage , 1996, Nature.

[17]  A. Michelson,et al.  A molecular aspect of hematopoiesis and endoderm development common to vertebrates and Drosophila. , 1996, Development.

[18]  E. Svensson,et al.  Long-term expression of erythropoietin in the systemic circulation of mice after intramuscular injection of a plasmid DNA vector. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[19]  E. Morrisey,et al.  GATA-6: a zinc finger transcription factor that is expressed in multiple cell lineages derived from lateral mesoderm. , 1996, Developmental biology.

[20]  D. Srivastava,et al.  Molecular Pathways Controlling Heart Development , 1996, Science.

[21]  M. Simon,et al.  Gotta have GATA , 1995, Nature Genetics.

[22]  S. Orkin,et al.  Functional synergy and physical interactions of the erythroid transcription factor GATA-1 with the Krüppel family proteins Sp1 and EKLF , 1995, Molecular and cellular biology.

[23]  D. Wilson,et al.  The GATA-4 transcription factor transactivates the cardiac muscle-specific troponin C promoter-enhancer in nonmuscle cells , 1994, Molecular and cellular biology.

[24]  C. Mueller,et al.  GATA-4/5/6, a subfamily of three transcription factors transcribed in developing heart and gut. , 1994, The Journal of biological chemistry.

[25]  Stuart H. Orkin,et al.  An early haematopoietic defect in mice lacking the transcription factor GATA-2 , 1994, Nature.

[26]  J. D. Engel,et al.  Embryonic expression and cloning of the murine GATA-3 gene. , 1994, Development.

[27]  D. Wilson,et al.  Localization of transcription factor GATA-4 to regions of the mouse embryo involved in cardiac development. , 1994, Developmental biology.

[28]  D. Thuerauf,et al.  Regulation of rat brain natriuretic peptide transcription. A potential role for GATA-related transcription factors in myocardial cell gene expression. , 1994, The Journal of biological chemistry.

[29]  J. Molkentin,et al.  Transcription factor GATA-4 regulates cardiac muscle-specific expression of the alpha-myosin heavy-chain gene , 1994, Molecular and cellular biology.

[30]  M. Nemer,et al.  A hormone-encoding gene identifies a pathway for cardiac but not skeletal muscle gene transcription , 1994, Molecular and cellular biology.

[31]  P. Simpson,et al.  pannier, a negative regulator of achaete and scute in Drosophila, encodes a zinc finger protein with homology to the vertebrate transcription factor GATA-1. , 1993, Development.

[32]  J. D. Engel,et al.  DNA-binding specificities of the GATA transcription factor family , 1993, Molecular and cellular biology.

[33]  S. Orkin,et al.  DNA-binding specificity of GATA family transcription factors , 1993, Molecular and cellular biology.

[34]  S. Orkin.  GATA-binding transcription factors in hematopoietic cells , 1992 .

[35]  S. Orkin,et al.  Erythroid differentiation in chimaeric mice blocked by a targeted mutation in the gene for transcription factor GATA-1 , 1991, Nature.